不同延迟降温时间对劳力型热射病大鼠病理损伤的影响

Effect of different delayed cooling time on organ injuries in rat models of exertional heat stroke

目的通过建立劳力型热射病(EHS)大鼠模型,探索不同降温时间对器官病理损伤的影响及可能的机制。方法选取健康成年雄性Wistar大鼠72只建立劳力型热射病动物模型。将大鼠随机分为6组,12只/组:正常对照组(CON);模型组(EHS)(建模后不进行主动降温);即刻降温组(建模后立即进行冷水浴降温);延迟降温A组(建模后延迟5 min进行冷水浴降温);延迟降温B组(建模后延迟15 min进行冷水浴降温);延迟降温C组(建模后延迟30 min进行冷水浴降温)。记录各组大鼠核心体温变化,计算降温速率。所有实验大鼠观察24 h后,解剖留取血液样本检测炎症指标白细胞介素-1β、白细胞介素-2、白细胞介素-4、白细胞介素-6、白细胞介素-10、γ-干扰素并进行脏器(肾脏、肺脏、大脑和回肠)病理学检查;若24 h内发生死亡,则立即解剖留取血液样本化验并进行病理取材。结果模型大鼠24 h内死亡例数随着降温治疗的延迟而增加,各组死亡率差异有统计学意义(P<0.05)。降温延迟时间与死亡率呈正相关(r=0.996,P=0.004)。降温速率与死亡率呈负相关(r=-0.961,P=0.009)。炎症因子检测结果显示,各因子在不同降温干预组的浓度变化呈现出较大的异质性。所有模型动物均有明显器官损伤,病理以上皮脱落、水肿、渗出和炎细胞浸润为主;脑组织和肾组织在发病24 h内受损最明显。结论EHS大鼠模型肾脏、肺脏、大脑和小肠存在显著的非特异性病理损伤,但受损程度并不一致;随着降温的延迟,病理损伤逐渐加重。炎症因子在不同降温时间干预的血浆浓度变化存在显著异质性。

Methods To investigate how the timing of cooling therapy affects organ injuries in rats with exertional heat stroke(EHS)and explore the possible mechanisms.Methods A total of 60 adult male Wistar rat models of EHS were randomized into model group without active cooling after modeling,immediate cooling group with cold water bath immediately after modeling,delayed cooling groups with cold water bath at 5,15 and 30 min after modeling,with another 12 mice without EHS as the normal control group.The changes in core body temperature of the mice were recorded and the cooling rate was calculated.After observation for 24 h,the mice were euthanized and blood samples were collected for detection of interleukin-1β(IL-1β),IL-2,IL-4,IL-6,IL-10,and interferon-γ,followed by pathological examination of the vital organs.The rats that died within 24 h were immediately dissected for examination.Results The number of deaths of the model rats within 24 h increased significantly with the time of delay of cooling treatment.The delay of cooling was positively correlated(r=0.996,P=0.004)while the cooling rate negatively correlated with the mortality rate(r=-0.961,P=0.009).The inflammatory cytokine levels presented with different patterns of variations among the cooling intervention groups.All the rat models of EHS had significant organ damages characterized mainly by epithelial shedding,edema,effusion,and inflammatory cell infiltration,and brain and renal injuries reached the peak level at 24 h after EHS.Conclusion EHS causes significant nonspecific pathologies of varying severities in the vital organs of rats,and the injuries worsen progressively with the delay of cooling.There is a significant heterogeneity in changes of serum inflammatory cytokines in rats with different timing of cooling intervention following EHS.